Reflex Sympathetic Dystrophy, or "RSD," is a common but poorly recognized chronic syndrome that most often occurs following traumatic injury to a limb. It is also associated with heart attack (myocardial infarction) and certain disorders of the nervous system. RSD includes disorders that were in the past known as causalgia, minor causalgia, post-traumatic pain syndrome, post-traumatic spreading neuralgia, post-traumatic vasomotor disorders, post-traumatic painful arthrosis, Sudeck's atrophy, sympathalgia, shoulder-hand syndrome, chronic traumatic edema, post-traumatic edema, autonomic hyper-reflexia, and reflex dystrophy, among others. (See: Bonica, J. J., The Management of Pain, Second Ed., Lea & Febiger, Philadelphia, 1990, pp. 220-243). The International Association for the Study of Pain continues to distinguish "causalgia," which is a more severe disorder often caused by nerve injury from war-inflicted shrapnel or projectile wounds, and which has some distinctive symptoms such as psychological disturbances that apparently result from the continuous, intense pain. However, most clinicians and researchers recognize that causalgia is symptomologically quite similar to the reflex sympathetic dystrophies, that it is treated in essentially the same way, and that it likely results from the same underlying mechanisms. Therefore, we hereinafter use the terms reflex sympathetic dystrophy and "RSD" to mean all of the above-mentioned disorders, including causalgia, as well as other disorders that fall within the symptomological definition of RSD.
RSD causes pain, stiffness, disturbances of the limb's blood vessels and muscles, and swelling. It is generally disabling because of the intensity of the pain. Also, since movement of the affected limb makes the pain much worse, patients suffering from RSD often stop using the affected limb at all. (Lankford, L. L., Reflex Sympathetic Dystrophy, in: Management of Peripheral Nerve Problems, G. E. Omer, Jr., and M. Spinner, eds; W. B. Saunders Co., Philadelphia, 1980; pp. 216-244.)
RSD often occurs following sprains, dislocations, and fractures of the hands, feet or wrists, and also following traumatic amputation of fingers, hands or wrists. However, the likelihood of developing RSD and its severity cannot be predicted based upon the severity of the injury; the disorder can even be caused by seemingly minor injuries such as contusions, cuts or even pinpricks to the fingers, hands, toes or feet. Following heart attacks, some patients develop a form of RSD known as "shoulder-hand syndrome," where the shoulder becomes painful and disabled, and the hand on the same side becomes painful and swollen.
Although many theories have been advanced, the mechanism that causes RSD is not clearly understood. One recent view is that RSD is caused by increased firing of peripheral nerves due to increased sensitivity, which in turn causes altered responses by the spinal cord, which then responds abnormally to signals from the brain stem and cortex. (See: Schwartzman, R. J. and T. L. McLellan, Reflex Sympathetic Dystrophy, Arch. Neurol. 44:555-561).
Unless successfully treated, RSD progresses through three stages of increasing disability. In Stage I, the "acute" phase, there is a burning or aching pain that is greater than the pain caused by the initial injury. The pain gets worse when the limb is touched, or when the patient becomes emotionally upset. The limb becomes swollen, hot or cold to the touch, and there is pronounced hair and nails growth. In Stage II, the "dystrophic" phase, the limb becomes hard and swollen, sweaty, and cool, and the hair begins to fall out. The nails become ridged, cracked and brittle. The pain becomes constant, and is increased by any stimulation of the limb. In Stage III, the "atrophic" stage, the pain spreads from the limb, and irreversible tissue damage occurs. The skin becomes thin and shiny, and the fingertips become wasted. The fingers may become permanently flexed, and X-rays show considerable bone loss. Id.
An important method for treating RSD is to temporarily block the sympathetic nerves of the affected limb. The sympathetic nerves are those that largely contain adrenergic fibers (i.e., those that use norepinephrine as a neurotransmitter), and which tend to depress secretion, decrease the tone and contractility of visceral smooth muscles, and cause the contraction of blood vessels. Such a blockade can be accomplished by injecting a local anesthetic such as lidocaine into the symapthetic nerve ganglia near the spinal cord that serve the affected limb. More commonly today, however, this is accomplished by making a local anaesthetic block of the affected limb. This is done by using a "Bier block." A Bier block is performed by elevating the limb and isolating it from the circulation using a tourniquet; the anesthetic is then injected into the limb intravenously, and left there for five to fifteen minutes. The tourniquet is then removed. This provides an effective sympathetic blockade, but without the inherent risks involved in injecting spinal ganglia.
Such regional local anesthetic blocks can be quite effective in treating RSD, particularly when carried out early in the course of the disorder. The response is generally prompt and dramatic; the anesthetic blocks the sympathetic nerves and also relaxes vascular smooth muscle, resulting in vasodilation and a reversal of the pain. The administration of repeated blocks over a period of time often improves the relief provided. It has been optimistically reported that such blockades combined with vigorous physical therapy can effect a "cure" for about 80% of patients with RSD. Binica, Supra. However, there are still at least 20% of patients who do not obtain complete relief. In addition, even among those who might otherwise obtain substantially complete relief by this method, good results depend upon prompt treatment.
Another method of considerable interest is the use of intravenous regional sympathetic block (IRSB) with the specific sympathetic nerve terminal blocking drug guanethidine. (IRSB is another term used to describe what is essentially a Bier block using a drug other than a local anaesthetic). Hannington-Kiff, J. G., "Antisympathetic drugs in limbs," in: Textbook of Pain, P. D. Wall and R. Melzak, eds., Churchill Livingstone, London, (1984), pp. 566-573. Guanethidine is a drug which displaces norepinephrine in presynaptic vesicles and prevents its reuptake. Many clinicians have reported good results and the achievement of long lasting pain relief using guanethidine IRSB. However, two double-blind comparisons failed to find any statistically significant difference between IRSB with guanethidine and IRSB with salt water (saline), calling into question the value of this therapy. Blanchard, J., S. Ramamurthy, N. Walsh, J. Hoffman, and L. Schoenfeld, "Intravenous Regional Sympatholysis: a Double-Blind Comparison of Guanethidine, Reserpine, and Normal Saline," Journal of Pain and Symptom Management (1990) 5(6):357-361; Jadad, A. R., D. Carroll, C. J. Glynn, and H. J. McQuay, "Intravenous Regional Sympathetic Blockade for Pain Relief in Reflex Sympathetic Dystrophy: A Systematic Review and a Randomized, Double-Blind Crossover Study," Journal of Pain and Symptom Management (1995) 10(1):13-20.
A third and more recent treatment for RSD is the oral administration of phenoxybenzamine, a potent drug which blocks postsynaptic .alpha..sup.1 receptors and also blocks presynaptic .alpha..sup.1 receptors. In the primary study of this therapy, increasing oral doses of this drug were administered to RSD patients until a maximum dosage of 40 to 120 mg was reached. This treatment was continued for 6 to 8 weeks. A complete cure was reported for all patients, and the authors concluded that treatment with oral phenoxybenzamine was simple, safe and effective. Ghostine, S. Y., Y. G. Comair, D. M. Turner, N. F. Kassell, and C. G. Azar, "Phenoxybenzamine in the Treatment of Causalgia," J. Neurosurg. (1984) 60:1263-1268. However, the authors reported that postural hypotension was a prominent side effect, which caused lightheadedness, and required some patients to wear leg stockinettes or an abdominal girdle throughout treatment. 17 out of 40 patients, or about 45%, were reported to have experienced hypotension. Some patients also reported ejaculatory problems. These side effects, particularly in view of the need to continue therapy for 6 to 8 weeks, substantially reduces the value of oral phenoxybenzamine for the treatment of RSD.